Our long-term objective is to ascertain how protein conformation plays a role in biological function and in various diseases.
Our specific aims are to treat the role of basic physical forces, key interactions, key residues, as well as the role of conformation, with an improved coarse-grained UNRES model, in several biological systems related to specific diseases. We will also continue the development of our UNRES model of nucleic acids (NARES-2P) and merge UNRES and NARES-2P into a viable package, which will be provided to the community. We will demonstrate how these aims can lead to valid predictions of structures and folding pathways of proteins, and protein-nucleic acid and protein-protein complexes. Our main focus will involve the application of this methodology to specific biological problems.

Public Health Relevance

As pointed out in the Project Summary, the long-term objective of this research is to ascertain how protein conformation plays a role in various diseases. Examples of such diseases in which conformation plays a role are sickle cell anemia and amyloid diseases such as Alzheimer's and mad cow disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM014312-58
Application #
8694188
Study Section
Macromolecular Structure and Function D Study Section (MSFD)
Program Officer
Wehrle, Janna P
Project Start
1977-01-01
Project End
2018-02-28
Budget Start
2014-06-02
Budget End
2015-02-28
Support Year
58
Fiscal Year
2014
Total Cost
$497,534
Indirect Cost
$172,533
Name
Cornell University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Rojas, Ana; Maisuradze, Nika; Kachlishvili, Khatuna et al. (2017) Elucidating Important Sites and the Mechanism for Amyloid Fibril Formation by Coarse-Grained Molecular Dynamics. ACS Chem Neurosci 8:201-209
Makowski, Mariusz; Liwo, Adam; Scheraga, Harold A (2017) Simple Physics-Based Analytical Formulas for the Potentials of Mean Force of the Interaction of Amino Acid Side Chains in Water. VII. Charged-Hydrophobic/Polar and Polar-Hydrophobic/Polar Side Chains. J Phys Chem B 121:379-390
He, Yi; Maisuradze, Gia G; Yin, Yanping et al. (2017) Sequence-, structure-, and dynamics-based comparisons of structurally homologous CheY-like proteins. Proc Natl Acad Sci U S A 114:1578-1583
Vila, Jorge A; Scheraga, Harold A (2017) Limiting Values of the one-bond C-H Spin-Spin Coupling Constants of the Imidazole Ring of Histidine at High-pH. J Mol Struct 1134:576-581
Krupa, Pawe?; Mozolewska, Magdalena A; Wi?niewska, Marta et al. (2016) Performance of protein-structure predictions with the physics-based UNRES force field in CASP11. Bioinformatics 32:3270-3278
Lipska, Agnieszka G; Seidman, Steven R; Sieradzan, Adam K et al. (2016) Molecular dynamics of protein A and a WW domain with a united-residue model including hydrodynamic interaction. J Chem Phys 144:184110
Cote, Yoann; Maisuradze, Gia G; Delarue, Patrice et al. (2015) New Insights into Protein (Un)Folding Dynamics. J Phys Chem Lett 6:1082-6
Mozolewska, Magdalena A; Krupa, Pawe?; Scheraga, Harold A et al. (2015) Molecular modeling of the binding modes of the iron-sulfur protein to the Jac1 co-chaperone from Saccharomyces cerevisiae by all-atom and coarse-grained approaches. Proteins 83:1414-26
Scheraga, Harold A (2015) My 65 years in protein chemistry. Q Rev Biophys 48:117-77
Rackovsky, S (2015) Nonlinearities in protein space limit the utility of informatics in protein biophysics. Proteins 83:1923-8

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